The influence of age on long-term synaptic plasticity will be studied int he striatum using in vitro brain slice and intracellular recording techniques. Synaptic efficacy will be monitored by sampling responses to paired stimuli. This procedure allows simultaneous monitoring of short- term, presynaptic changes in release and long-term tetanus induced changes in synaptic efficacy. Correlations will then be performed between paired- pulse and long -term synaptic plasticity. Each hypothesis will be tested under conditions that increase the probability of inducing LTD and, in a separate set of experiments, LTP. Initially the effect of senescence will be established for LTD and LTP. The second specific aim will then test the hypotheses that 1) inrinsic dopamine (DA) released in in vitro slices modulates synaptic plasticity in the striatum, and 2) that this modulation declines with age. DA will be depleted through unilateral 6-OHDA lesions to the substantia nigra (SNc). Lesion effects will be determined through comparisons to the contralateral (DA intact) striatum. DAergic modulation of synaptic plasticity will then be studied DA perfusion of slices ipsilateral to the 6-OHDA lesion. Since intrinsic release will be eliminated in these slices, dose-response comparisons can be made between age-groups. This procedure thus allows us to test the hypothesis that age-dependent differences in DA receptor activation alter DA modulation of synaptic plasticity. DA depletion will be quantified by calculating loss of tyrosine hydroxylase positive neurons in the SNc and measurements of DA content int he striatum (HPLC). The third specific aim will test the hypotheses that 1) long-term synaptic plasticity is triggered by tetanus induced transients in intracellular Ca2+ and that 2) this process is altered by age-related changes in Ca2+ homeostasis. Two complementary procedures will be used to differentiate between the role of pre- and postsynaptic fluxes of Ca2+. First, brain slices will be exposed to a low Ca2+ solution that will reduce Ca2+ influx uniformly in pre-and postsynaptic compartments. These result will be compared with 1) data from slices bathed in normal Ca2+ and 2) data obtained when only postsynaptic Ca2+ is lowered through intracellular injection of BAPTA. The fourth specific aim will determine if synaptic plasticity int he striatum is related to cell classification and location in the calbindin D28K defined 3-dimensional patch-matrix system. The final goal of this proposal will be to determine if age-related alterations in motor performance are correlated with underlying deficits in striatal synaptic plasticity. In total, these studies will provide a novel electrophysiological framework for interpreting basal ganglia-related changes in motor performance in aging.